Year: 2026
Type: preprint
Abstract: Within the mechanistic realm of centralized catalysis (chemical catalysis), reactivity activation is site-centered on reactant functional groups and site-driven from catalytic centers, leading to a low-resolution catalytic architecture with low catalytic activity and catalytic efficiency. In contrast, within the mechanistic realm of decentralized catalysis (biological catalysis), reactivity activation is reactant-spanned on both functional groups and appendage groups and enclosure-driven from catalytic cavity, offering a high-resolution catalytic architecture with high catalytic activity and catalytic efficiency. Herein, as a proof-of-concept illustration for reactant-spanned and enclosure-driven enzymatic catalysis (as exemplary for biological catalysis), we report the engineering of a carboxylesterase for acyl transfer from carboxylesters to amines. The precision disjoint presentation activation of acyl group and amino group has empowered the achievement of an expansive reactant scope of both carboxylesters and amines. As a demonstration of the synthetic utility, a pharmaceutically relevant agent has been constructed on the gram scale. As a manifestation of the synthetic potential, a quantitative or near-quantitative S-enantioselectivity has been established for the kinetic resolution of secondary amines. The high catalytic activity and catalytic efficiency showcased herein promise decentralized catalysis as a powerful, generic mechanistic basis for the highly effective programming of reactivity activation. Keywords: Centralized Catalysis; Decentralized Catalysis; Chemical Catalysis; Biological Catalysis; Carboxylesterase; Acyl Transfer; Carboxylester; Amine; Kinetic Resolution.
Source: ChemRxiv
Institution: Nanjing University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G117299061, G6916446599
OpenAlex ID: W7212030657